Basement membranes are ubiquitous structures which are thought to be synthesized by several normal cell types including epithelial, endothelial, smooth muscle, Schwawn cells, and their derivatives. However, the transformed malignant counterparts of these cells, carcinomas and sarcomas, generally loose their ability to synthesize basement membranes and instead acquire basement membrane-degradative properties via the secretion of different families of proteases including metalloproteinases, serine proteinases and thiol proteinases.
Because of the almost universal inability of human tumors to produce basement membranes, studies designed to investigate tumor cell interactions with basement membranes have relied heavily upon utilizing matrix derived from the unusual non-metastasizing Engelbreth-Holm, Swarm ("EHS") tumor. The EHS tumor matrix is rich in laminin, type IV collagen, nidogen and heparin sulfate proteoglycan, as well as the small matrix glycoprotein BM-40. These molecules have been extracted individually and as an unfractionated extract which reconstitutes to form a three-dimensional gel ("Matrigel" containing entrapped growth factors. This reconstituted basement membrane has been used extensively to study cellular differentiation, tumor cell invasion, angiogenesis and tumorigenicity. The coinjection of tumor cells and matrigel enables the in vivo growth of several otherwise non-tumorigenic cells and greatly stimulates the growth of a wide variety of primary and established tumor cells of both human and murine origin. However, matrigel has failed to support the growth of many primary human cancers, including prostatic and breast carcinoma. It is therefore of substantial interest to develop basement membrane compositions of human origin having human proteins and factors for the investigation of human tumors and to act as a source of basement membrane components.